Primary Outcome Results of the Preventing Epilepsy Using Vigabatrin in Tuberous Sclerosis Complex Infants (PREVeNT Trial)

Abstract number : 1.283
Submission category : 7. Anti-seizure Medications / 7B. Clinical Trials
Year : 2023
Submission ID : 335
Source : www.aesnet.org
Presentation date : 12/2/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Darcy Krueger, MD, PhD – Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Jurriaan Peters, MD, PhD – Boston Children's Hospital; Brenda Porter, MD, PhD – Stanford University; Tarrant McPherson, PhD – Emory University; Sarah O'Kelley, PhD – University of Alabama Birmingham; Mustafa Sahin, MD, PhD – Boston Children's Hospital; Katherine Taub, MD – Children's Hospital of Philadelphia; Rajsekar Rajaraman, MD – University of California Los Angeles; Stephanie Randle, MD – Seattle Children's Hospital; William McClintock, MD – Children's National Hospital; Mary Koenig, MD – Univesity of Texas Houston; Michael Frost, MD – Minnesota Epilepsy Group; Hope Northrup, MD – Univesity of Texas Houston; Klaus Werner, MD, PhD – Duke University; Danielle Nolan, MD – Beaumont Children's Hospital; Michael Wong, MD, PhD – Washington University St. Louis; Jessica Krefting, RN – University of Alabama Birmingham; Fred Biasini, PhD – University of Alabama Birmingham; Kalyani Peri, MS – University of Alabama Birmingham; Gary Cutter, PhD – University of Alabama Birmingham; E Martina Bebin, MD, MPH – University of Alabama Birmingham

Epilepsy is highly prevalent in Tuberous Sclerosis Complex (TSC), with two thirds experiencing onset within the first year of life and overall life-time prevalence greater than 80%. Most will become refractory to all medical treatments currently available available and have associated neurodevelopmental and behavioral disorders. The PREVeNT clinical trial was conducted to test the hypothesis that early vigabatrin in infants diagnosed with TSC, when initiated prior to the onset of seizures, would improve neurocognitive outcome at 24 months of age.
We conducted a Phase IIb multicenter randomized double-blind placebo-controlled trial of vigabatrin at first epileptiform EEG (early treatment) vs. vigabatrin at seizure onset (conventional treatment) in infants with TSC. The primary outcome measure was the Bayley-III cognitive assessment score at 24 months. Secondary outcomes included the prevalence of drug resistant epilepsy, additional standardized measures of learning and neurodevelopment, and assessment of vigabatrin safety in this population.

Of eighty-four infants enrolled, 12 were screen failures, 12 had normal EEGs throughout and were never randomized, and 4 went straight to open-label treatment with vigabatrin due to detection of electrographic seizures on first EEG.  The remaining 56 met randomization criteria to begin treatment with early vigabatrin (n=29) or placebo (n=27) upon first detection of abnormal epileptiform activity on EEG.  Within the randomized cohort, 19 of 27 in the placebo arm transitioned to open label vigabatrin with a median delay of 44 days after randomization. Bayley-III cognitive scaled scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes.  Adverse events were also similar between groups. The only significant difference detected comparing early versus conventionally treated infants was a lower incidence of infantile spasms and time to spasms onset after randomization in the early treatment group.

Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor delay onset or lower the incidence of focal seizures and drug resistant epilepsy at 24 months. Preventative vigabatrin is associated with later time to onset and lower incidence of infantile spasms.

This study is registered at clinicaltrials.gov (NCT02849457). Funding and material support for this study was provided by the NIH National Institute of Neurological Diseases and Stroke (U01-NS092595), NIH National Center for Advancing Translational Sciences (UL1-TR001425), TSC Alliance, Bcureful, Pediatric Epilepsy Research Foundation, and Lundbeck Pharmaceuticals.

Anti-seizure Medications